1. Field of Invention
The current patent application generally relates to medical image processing.
2. Discussion of Related Art
The ultimate goal of new cancer therapies is cure. A good cancer treatment should ideally prolong survival while preserving a high quality of life cost-effectively. To demonstrate prolonged survival in a clinical trial in some more slowly progressing cancers can take 5-10 years or longer. Such trials are expensive, not only in cost but in time.
The typical development pathway for cancer therapeutic drugs includes an evolution from phase I to phase II and to phase III clinical trials. In phase I trials, toxicity of the agent is typically assessed to determine what dose is appropriate for subsequent trials. Typically, the statistical power of phase I drug trials is inadequate to assess antitumor efficacy. In phase II trials, evidence of antitumor activity is obtained. Phase II trials can be done in several ways. One approach is to examine tumor response rate versus a historical control population treated with an established drug. New drugs with a low response rate are typically not moved forward to advanced clinical testing under such a paradigm. In such trials, tumor response has nearly always been determined anatomically. An alternative approach is to use a typically larger sample size and have a randomized phase II trial, in which the new treatment is given in one treatment arm and compared with a standard treatment. Once drug activity is shown—or suggested—in phase II, phase III trials are typically performed. Phase III trials are larger and typically have a control arm treated with a standard therapy. Not all phase III trials are successful, but all are costly.
Determining which innovative cancer therapeutics should be advanced to pivotal large phase III trials can be unacceptably delayed if survival is the sole endpoint for efficacy. Survival trials can also be complicated by deaths due to nonmalignant causes, especially in older patients in whom comorbidities are common. Additional complexities can include patients who progress on a clinical trial but who go on to have one of several nonrandomly distributed follow-up therapies—which can confound survival outcomes.
Therefore, there is great interest in surrogate metrics for survival after investigational cancer treatments, such as response rate, time to tumor progression, or progression-free survival. Changes in tumor size after treatment are often, but not invariably, related to duration of survival. To this end, a variety of approaches to measuring response rate have been developed, beginning with the original reports by Moertel on physical examination in 1976 and continuing to the subsequent World Health Organization (WHO) criteria (1979), Response Evaluation Criteria in Solid Tumors (RECIST) (2000), and RECIST 1.1 (2009). These approaches typically focus on how often a tumor shrinks anatomically and defined such response in several ways, including, for example. complete response, partial response, stable disease, and progressive disease. This type of classification divides intrinsically continuous data (tumor size) into 4 bins, losing statistical power for ease of nomenclature and convenience.
Thus, intrinsic limitations of currently applied anatomic tumor response metrics, including WHO, RECIST, and the new RECIST 1.1 criteria, led to on-going pursuit for quantitative and qualitative approaches to investigate surrogate endpoints based on functional imaging such as Positron Emission Tomography/Computed Tomography (PET/CT). In particular, a framework for PET Response Criteria in Solid Tumors (PERCIST, version 1.0) has been recently proposed. These functional surrogate endpoints may be useful in future multicenter trials and may serve as a starting point for further refinements of quantitative PET response. They may also provide some guidance for clinical quantitative structured reporting on individual patients. Thus, there is a need in the art for a method that can be objectively implemented by different users in a multi-center environment to monitor a patient's condition over time (i.e., in a longitudinal manner).